The PERMIT guidelines for designing and implementing all stages of personalised medicine research

Abstract

Personalised medicine (PM) research programmes represent the modern paradigm of complex cross-disciplinary research, integrating innovative methodologies and technologies. Methodological research is required to ensure that these programmes generate robust and reproducible evidence. The PERMIT project developed methodological recommendations for each stage of the PM research pipeline. A common methodology was applied to develop the recommendations in collaboration with relevant stakeholders. Each stage was addressed by a dedicated working group, specializing in the subject matter. A series of scoping reviews that mapped the methods used in PM research and a gap analysis were followed by working sessions and workshops where field experts analyzed the gaps and developed recommendations. Through collaborative writing and consensus building exercises, the final recommendations were defined. They provide guidance for the design, implementation and evaluation of PM research, from patient and omics data collection and sample size calculation to the selection of the most appropriate stratification approach, including machine learning modeling, the development and application of reliable preclinical models, and the selection and implementation of the most appropriate clinical trial design. The dissemination and implementation of these recommendations by all stakeholders can improve the quality of PM research, enhance the robustness of evidence, and improve patient care.

Fig. 1

The personalised medicine research pipeline: Stage 1 – Collection of patient and omics data: collection of patient data, including –omics data, through retrospective and/or prospective cohorts. Stage 2 – Machine learning (ML) stratification: Use of patient data to stratify the patient population into homogeneous clusters, through either conventional statistical or ML methods. Stage 3 - The translational development: Assessing the efficacy and safety of the treatment options in preclinical models is often required. Stage 4 - Clinical trials - therapeutic solutions are tested in the various patient clusters, and the effectiveness of the personalised vs. non-personalised approach can be assessed.

Fig. 2

Common methodological framework of the PERMIT Project.